This project is designed to test the hypothesis that bacterial products, which produce acute and chronic systemic inflammation and inflammatory changes in the distal small intestine of susceptible hosts, act in part through activation of the kallikrein-kinin system. further, this study will determine if the kallikrein-kinin system is involved in the pathogenesis of experimentive inflammatory bowel disease (IBD). This plasma proteolytic enzyme system is a source of excellent candidate mediators since the reactions release bradykinin from high molecular weight kininogen (HK) which can produce edema, vascular permeability and pain, and generate kallikrein, which can cause neutrophil activation and chemotaxis. The specific aims are: 1) To ascertain whether acute inflammation induced by systemically injected PG-PS is mediated by activation of the kallikrein- kinin system in rats by investigating the ability of contact system inhibitors to prevent the arthritis and the biochemical changes. 2) To ascertain whether activation of the kallikrein-kinin system accompanies indicators of acute inflammation by PG-PS and/or LPS and whether inhibitors will prevent pathologic and biologic changes. 3) To investigate whether the induction and reactivation of experimental granulomatous enterocolitis in rats is accompanied by activation of the kallikrein-kinin system and whether inhibition will prevent the pathologic and biochemical changes. 4) To determine if contact activation occurs with reactivation and colonic injury models. These models in rats mimic the extraintestinal manifestations and bowel changes of IBD and will evaluate the participation of the kallikrein-kinin system and therapeutic potential of specific inhibitors.